Pinnaic acids

Three novel related marine alkaloids, halichlorine (1148) from the sponge Halichondria okadai (1177, 1178) and pinnaic acid (1149) and tauropinnaic acid (1150) from the bivalve Pinna muricata (1179), have been the objects of much synthetic interest in view of their pronounced biological activity (inhibition of the vascular cell adhesion molecule-1) (1180). Synthesis of these alkaloids led to both revision and confirmation of the original structures (1181,1182). The syntheses of the previously known chlorine-containing cylindricines have been reviewed (1183). 

Chou T, Kuramoto M, Otani Y, Shikano M, Yazawa K, Uemura D (1996) Pinnaic Acid and Tauropinnaic Acid Two Novel Fatty Acids Composing a 6-Azaspiro[4.5]decane Unit from the Okinawan Bivalve Pinna muricata. Tetrahedron Lett 37 3871... 

Carson MW, Kim G, Danishefsky SJ (2001) Total Synthesis and Proof of Stereochemistry of Natural and Unnatural Pinnaic Acids A Remarkable Long-Range Stereochemical Effect in the Reduction of 17-Oxo Precursors of the Pinnaic Acids. Angew Chem Int Ed 40 4453... 

The fatty acid-derived alkaloids halichlorine (112) [99,100], pinnaic acid (113), and tauropinnaic acid (114) [101,102] have novel structures and unique anti-inflammatory activity. 

Pinnaic Acids and Halichlorine Anti-inflammatory Agents... 

The molecular complexities of these architecturally novel alkaloids have prompted intense studies to elaborate new and efficient methods and strategies for the synthesis of these products. Hence, several stereocontrol approaches have been developed to successfully construct the azaspirocyclic core of pinnaic acids and halichlorine, providing access to the formal total synthesis and highly stereoselectivity of these molecules (Christie et al. 2004 Zhang et al. 2005 Andrade and Martin 2005 Clive et al. 2005 and references cited therein). In particular, Danishefsky s research group has reported the first total synthesis of halichlorine (Trauner et al. 1999), supporting the previous conclusions regarding the structure of this alkaloid (Kuramoto et al. 1996 Arimoto et al. 1998), and has... 

Figure 18.5. Chemical structures of halichlorine (a) and pinnaic acids (b).

Andrade, R.B., and Martin, S.F. 2005. Formal syntheses of (+/-)-pinnaic acid and (+/-)-halichlorine. Org Lett 7, 5733-5735. Arimoto, H., Hayakawa, I., Kuramoto, M., and Uemura, D. 1998. Absolute stereochemistry of halichlorine a potent inhibitor ofVCAM-1 induction. Tetrahedron Lett i9, 861—862. 

Carson, M.W., Kim, G., and Danishefsky, D.J. 2001. Total synthesis and proof of stereochemistry of natural and unnatural pinnaic acids a remarkable long-range stereochemical effect in file reduction of 17-oxo precursors of the pinnaic acids. Angew Chem Int Ed Engl 40, 4453-4456. 

Tong, C., Kuramoto, M., Otani, Y, Shikano, M., Yazawa, K. and Uemura, D, 1996. Pinnaic acid and tauropinnaic acid two novel fatty acids composing a 6-azaspiro[4.5]decane unit from the Okinawan bivalve Pinna muricata.. Tetrahedron Lett 37, 3871-3874. 

Zhang, H.L., Zhao, G., Ding, Y, and Wu, B. 2005. An efficient and enantioselective approach to the azaspirocyclic core of alkaloids formal synthesis of halichlorine and pinnaic acid. J Org Chem 70, 4954-4961. 

The diene 11 was used in a synthesis of the anti-inflammatory agent pinnaic acid. Suggest a method to prepare the alkenyl stannane 10 and reagents for the steps from 10 to the diene 11. 

Synthetic chemistry of halichlorine (15-membered lactone possessing indolizidine fragment) and the pinnaic acids 05CRV4514. 

Figure S.1 Structures of pinnaic acid and halichlorine Scheme 5.14 Beckmann reaction optimization.

Toward the Total Synthesis of Pinnaic Acid and Halichlorine... 

The Beckmann rearrangement reaction was a key step in the total synthesis of two marine natural products, pinnaic acid (52) and halichlorine (53) IFigure 5.1T ° Pinnaic acid and halichlorine are of interest because they exhibit anti-inflammatory effects through inhibition of a cytosolic 85 kDa phospholipase (CPLA2) in vitro. Halichlorine is also a promising... 

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